Understanding Peripheral Arterial Disease: Causes, Symptoms, and Treatment

Peripheral arterial disease (PAD) is a common, yet under-diagnosed, systemic condition. It affects more than 200 million people worldwide, and prevalence is rising with the increase in global longevity and the epidemic of diabetes mellitus. In the Western world, the most common cause of PAD is atherosclerosis. The earliest symptom of PAD is usually muscle fatigue or pain in the lower extremities during walking, which is relieved by rest (termed intermittent claudication). By definition, PAD is a narrowing or occlusion of arteries distal to the aortic bifurcation. It is a cause of considerable morbidity and mortality and is also associated with a high risk of coronary artery disease (CAD) and cerebrovascular disease. However, despite the high cardiovascular risk in these patients, secondary prevention and risk factor modification are often suboptimal. PAD is a marker for systemic atherosclerosis, and these patients should be managed in concert with their increased global cardiovascular risk.

Causes of Peripheral Arterial Disease

Blood flows through the arteries to nourish the body. A reduction in blood flow can lead to less oxygen being delivered to the cells. The plaque in the arteries of a person with atherosclerosis is also at risk of breaking off and forming a blood clot. A blood clot can completely block the blood flow to the cells further down the artery and cause death of cells. This final scenario often occurs in the legs and is what causes the pain in the muscles that is characteristic of intermittent claudication.

In a person with a healthy artery, the innermost layer of the artery is smooth and thin, allowing blood to flow through the artery easily. With the onset of atherosclerosis, this layer becomes damaged and plaque starts to build. Over time, the plaque hardens and narrows the artery. This reduces and limits blood flow to the muscles and other cells.

The cause of peripheral artery disease is the result of atherosclerosis, a process where the arteries become blocked. Although there are several factors that contribute to the development of atherosclerosis such as diabetes, high blood pressure, and smoking, the process of atherosclerosis is the same for everyone. It occurs when a sticky material called plaque builds up in the arteries.


Atherosclerosis occurs when the peripheral blood vessels clot or become narrow due to the invasion and accumulation of white blood cells. It is a greater problem in diabetics and older people. This process begins with damage to the lining of the blood vessels. The damage causes a reaction of the cells in the vessel, which leads to a deposition of fatty substances. Once in the vessel, these fatty substances are toxic to the vessel and initiate a complex series of events to attempt to rid the vessel of these offending substances. Unfortunately, the process long term serves only to worsen the buildup of fatty substances. This is because the continuous reaction of cells in the vessel activates the blood’s platelets (clotting cells), and this leads to the adherence of more white blood cells. The end result of these events is the establishment of an atheroma composed of cholesterol and fatty substances covered in scar tissue in the vessel, which then decreases blood flow. This entire process greatly interferes with the ability of the vessel to dilate (increase in size) to increase blood flow. High sugar levels in diabetics cause a thickening of the blood and adverse changes to the blood vessel. This greatly exacerbates the problems of atherosclerosis in diabetics and can lead to a rapid worsening of PAD.


Diabetes is defined as an inability to utilize sugars in the body due to a breakdown in insulin, whose job it is to break down sugars after meals. There are 2 types of diabetes: in type 1 diabetes, the body doesn’t produce insulin, and in type 2, the insulin that is produced does not work properly. Both types of diabetes increase the risk of developing peripheral arterial disease, as there is an increased level of fatty deposits in the blood due to raised blood sugar levels. High sugar levels and high fat levels in the blood both contribute to the hardening and narrowing of the arteries, which is the main cause of peripheral arterial disease. High blood sugar levels also damage the blood vessels in the legs and feet and unwillingly contribute to the onset of peripheral arterial disease.
Diabetic patients are also more likely to develop complications with peripheral arterial disease more quickly than non-diabetics. This is due to the already damaged blood vessels in their legs and feet. Although treatment is the same for non-diabetics as it is for diabetics, diabetics may be unsuitable for some procedures or surgery due to their condition, so it is important to monitor their symptoms regularly.

High Blood Pressure

Hypertension or high blood pressure can lead to peripheral arterial disease and can also worsen an already existing PAD. It is important to maintain a normal blood pressure and, when necessary, to lower elevated blood pressure for the prevention and treatment of PAD. High blood pressure is defined by a sustained high force of blood against the walls of the arteries. This force will cause damage to the walls of the arteries and also cause tears and scrapes to the endothelial lining. When this occurs, cholesterol will form plaques to repair the damage to the arteries. High blood pressure will increase the occurrence of atherosclerosis. It can also cause damage to the kidneys. This is significant in PAD patients because many are diabetic and/or have atherosclerosis, and the kidney damage caused by high blood pressure will worsen the already existing conditions. Data from the Hammersmith Cohort Study, a follow-up study of patients who were investigated for a possible diagnosis of intermittent claudication, showed that hypertension was a strong risk factor for developing intermittent claudication.
In this study, the control group was 1234 randomly selected individuals from the local population, and the cases were 248 patients with claudication. Significantly more cases were found to be hypertensive, and the 10-year incidence of developing claudication was 10.7% in hypertensive patients as opposed to only 3.5% in normotensive patients. This study concluded that hypertensive patients are at a 3-fold risk of developing claudication compared to those with normal blood pressure. High blood pressure will also complicate treatment for PAD and will increase the need for invasive revascularization techniques.

Symptoms of Peripheral Arterial Disease

Slow-healing wounds can cause significant morbidity in patients affected by P.A.D. As a result of the restricted blood flow, minor injuries can develop into severe infections, ulcers, and in the worst-case scenario, gangrene. This is due to the lack of nutrients and oxygen needed to heal the tissue. It is estimated that between 5-10% of people with P.A.D. have critical limb ischemia at any one time. This is the severe obstruction of arteries which significantly reduces blood flow to the extremities and can lead to ulcers and sores that do not heal.

Numbness or weakness is another symptom of P.A.D. and is caused by the decreased blood flow to the affected area. If the blood flow is not restored, the loss of oxygen to the body tissue can cause the death and loss of function of that area. This is a severe complication as often times irreparable damage is done. This can significantly affect the quality of life and can cause disability in some patients.

Leg pain and cramping happen to be the common symptoms of Peripheral Arterial Disease (P.A.D.). This is because when one is active, the muscles need increased blood flow, which is not able to occur in the events of P.A.D. The pain can cause difficulty in walking, thus causing the claudication or limping effect. This symptom is usually located in the muscles of the feet and legs. The severity of the pain can range from mild discomfort to debilitating pain. It is said that one of the main problems with P.A.D. is that because the person affected can still get around, they attribute the pain to aging and lack of exercise. This delayed assessment of pain can exacerbate the disease and cause other symptoms to occur.

Leg Pain and Cramping

Intermittent claudication is pain in the leg at rest and caused by muscle ischemia. It is present in 1-2% of people aged 45-50 years, but in 20% of those aged 75 years. Intermittent claudication is the most benign form of PAD, but its recognition is important because it predicts an increased risk of cardiovascular events and death. It is usually due to aortoiliac or femoral artery disease, rather than disease of the more distal arteries. The clinical manifestation of claudication varies with the site of arterial narrowing and the degree of muscle ischemia. Claudication in the calves on walking uphill or at an incline is often due to aortoiliac disease because of the increased oxygen requirements of the hip and thigh muscles. Patients with femoral or popliteal artery disease often get calf pain on walking over short distances. Claudication in the hip or thigh muscles alone is less common, but may be seen in proximal adductor canal or external iliac artery disease. When disease is very severe, or there is a proximal total occlusion with poor collaterals, patients may get muscle pain at rest, which is relieved by hanging the leg over the side of the bed (so-called ‘dependent’ ache). This occurs because gravity increases blood flow to the ischemic muscle. Chronic muscle ischemia leads to muscle wasting and weakness, but very rarely limb ischemia may cause acute limb-threatening gangrene if there is associated severe infection of ischemic ulcers.

Numbness or Weakness

If you have been experiencing leg cramping or pain, especially during physical activity, and it is accompanied by numbness or weakness, you could be showing a sign of P.A.D. The pain occurs because your muscles are not getting enough blood and oxygen to meet the demands of the activity. When you stop the activity, the muscles can still feel pain for a short time as increased oxygen is demanded to rid the muscles of built-up waste products. It is a sign of critical limb ischemia, described above, which can be limb-threatening and should be given medical attention sooner rather than later. Whether the pain is simply discomforting or severe, it is not a symptom that should be dismissed as simply ‘overdoing it’. Failure to address the underlying problem and make a diagnosis in this stage could make the difference between partial recovery and amputation.
If pain extends to walking short distances, leading to the use of a cane or limp to support your mobility, it is a sign that the muscles in the leg are not getting enough of the energy source, glycogen. This occurs when pain is severe enough that you have adjusted your lifestyle to avoid the pain and no longer exert the energy to use the muscles. This is a clear indication of poor blood flow and should be examined by a medical professional.

Slow Healing Wounds

Impaired circulation often leads to sores or wounds on the feet or legs. The severity of these sores can range from superficial wounds, which heal relatively quickly upon correction of the blood flow problem, to deep, infected wounds which heal poorly. People with diabetes, who often develop neuropathy, are at even greater risk for amputation because the body no longer recognizes the extent of the damage since the “pain signals” have been turned off. In a worst-case scenario, an amputation may be necessary. It is important to remember that poor circulation does not develop overnight; it is the result of a progressive condition that can be managed and treated effectively to prevent worsening symptoms and lower the risk of amputation.
People with symptomatic PAD have a 10-fold greater risk of developing amputations and have a higher mortality rate than the general population. An early comprehensive intervention can reduce the incidence of amputation to less than 1% of claudicants and can improve the patient’s survival.

Coldness in the Affected Area

Ischemia reduces or stops blood flow to a part of the body. When blood flow is stopped, the affected area becomes cold. The description of “feeling like a cold” is a clear indication of not enough blood reaching the tissues. These symptoms indicate the potentially serious nature of PAD. Coldness can be particularly noted in one foot compared to the other. In addition to the symptom of coldness, the affected foot or leg may also experience a change in skin color to a bluish pale. This can become the resting color for the foot skin without necessarily darkening to the point of skin ulcer development. Skin hair may also stop growing where there is hair loss in an area. This is often referred to as a foot or area being “bald”. All these symptoms are indicative of chronic tissue damage that can potentially lead to limb loss.

4. Treatment Options for Peripheral Arterial Disease

Several medications have been proven to be beneficial in the treatment of PAD. Cilostazol is a phosphodiesterase III inhibitor that is known to be effective in increasing the distance that patients can walk before the onset of intermittent claudication. A randomized clinical trial involving 1902 patients with PAD found that cilostazol was superior to placebo in improving walking distances and was associated with better general health perception. High blood pressure should be treated. The use of ACE inhibitors has been proven to reduce cardiovascular events and increase walking times in patients with PAD. Statins should be used to lower cholesterol in all patients with PAD even those without hyperlipidemia as they have been shown to reduce cardiovascular events and improve walking distance. The use of antiplatelet agents is recommended to reduce the incidence of myocardial infarction and stroke.


This treatment is mandatory for all patients with PAD. Patients should be educated about their disease and the options for treatment. Aggressive risk factor modification should be employed to reduce the elevated cardiovascular risk that patients with PAD face. The most important aspect of the treatment of PAD is perhaps the modification of cardiovascular risk factors. Encouraging patients to stop smoking cannot be overstressed. Discontinuation of smoking can lead to symptomatic improvement in intermittent claudication because of improved collateral blood flow. Unfortunately, the magnitude of smoking cessation is underestimated by physicians. A recent study suggested that former smokers may even have better functional status than those who never smoked. MESSAGE: Smoking is the strongest and most easily modified risk factor that is associated with the development of peripheral arterial disease (PAD) and it is important that all patients are counseled to quit. High blood pressure should be treated with lifestyle modifications and medications. High cholesterol also needs to be treated with diet and exercise in addition to medications. An exercise program aiming for 30-45 minutes of walking at least 3 times a week is recommended for all PAD patients and can lead to a significant improvement in symptoms. All patients with PAD should also be on a healthy diet in order to reduce cardiovascular risk.

Lifestyle Changes

Lifestyle Changes

Furthermore, making these changes can help other treatments work better or be more effective. It’s important to make a lifelong commitment to heart-healthy lifestyle changes. In one of the largest studies of its kind, people who were at high risk for heart disease were able to lower their risk of having a heart attack or stroke by making lifestyle changes for 10 years. These same lifestyle changes can help people with PAD.

By far, the best and most effective treatment for PAD is to make a commitment to heart-healthy lifestyle changes. These changes may be the only treatment needed for those in the earliest stages of PAD. For others, a heart-healthy lifestyle can help prevent or slow the progression of PAD. If lifestyle changes are the only treatment needed, they may eliminate the need for further treatment.


Cholesterol has no symptoms, and the only way to know if it is at a healthy level is to have a blood test. A healthy level for blood cholesterol is less than 5mmol/L, or less than 4mmol/L for those at high risk of PAD. High cholesterol can be treated with a type of medication called a statin. Statins work by reducing the amount of cholesterol made by the liver and are effective at reducing blood cholesterol and the risk of heart attack or stroke.

One of the problems that can lead to atherosclerosis is high blood cholesterol. Cholesterol is a type of fat that is found in the blood. The body uses a small amount of cholesterol to carry out its normal functions – for example, it is used to repair cell membranes. The liver can also produce cholesterol to fulfill the body’s needs. However, too much cholesterol in the blood can increase the risk of atherosclerosis. This occurs because cholesterol and its related fats can build up in the artery walls to form plaque. Plaque can cause the arteries to narrow and harden, which in turn can reduce blood flow to the muscles and other tissues. If a piece of plaque breaks off from the artery wall, it can also cause a blood clot to form, which can further reduce blood flow.

The medications for PAD work by addressing various problems that contribute to the development of atherosclerosis. By doing so, they can help to slow or stop disease progression, and in some cases, they can also improve the symptoms.

Angioplasty and Stenting

Peripheral artery disease (PAD) occurs due to the buildup of plaque in the arteries carrying blood to the head, organs, and limbs. If you have PAD, you are at increased risk for heart attack and stroke. In severe cases, a procedure to surgically bypass a leg artery may be necessary. This involves using a healthy blood vessel from another part of the body to divert flow, to increase blood flow and oxygen to the affected area. This is known as peripheral artery bypass surgery. However, one of the most commonly utilized procedures to open up an artery clogged by an atherosclerotic plaque is angioplasty. During angioplasty, a thin catheter is inserted into the leg, through to the diseased artery in the leg. The catheter has a small balloon on the tip. Once the catheter is in place, the balloon is inflated to push the plaque to the sides of the artery, thereby opening up the vessel and improving blood flow to a leg. A comparison of angioplasty with stent vs. reality is that with angioplasty alone, there is a higher chance of the plaque clogging the artery again. By placing a stent in the artery after using the balloon, the mechanical help to open up the vessel can be sustained and the chances of the artery remaining open and blocked from debris dislodging from the initial procedure are higher than with angioplasty alone.

Bypass Surgery

Bypass surgery is a procedure used to treat more advanced disease involving large and medium arteries. It involves sewing a piece of healthy vein harvested from the patient’s leg or with a synthetic graft, to channel blood around the diseased or blocked artery. This procedure can be effective at reducing symptoms and improving blood flow to the affected limb, but it also carries significant risk and discomfort. It is usually reserved as a last resort for patients with chronic limb-threatening ischemia who are not suitable for endovascular treatment or who are not expected to achieve satisfactory results with angioplasty. High-quality randomized trials comparing bypass surgery with angioplasty are few, but due to advances in technology, the less invasive form of treatment is becoming a more widely accepted choice for patients and physicians. In a study to compare the two treatments, it was reported that bypass surgery is associated with higher long-term survival and a lower rate of limb amputation. However, there was a higher rate of non-lethal complications and a longer hospital stay. This study also suggested that quality of life and functional outcome are similar after both treatments.

This section describes the different treatment options available for PAD sufferers. The cost-to-benefit ratio for treatment of this disease is very high. Even with advanced disease, two-thirds of the patients are treated without surgical revascularization. Procedural options depend on the patient’s overall medical condition, the location and length of the blockage, and the availability of a saphenous vein for use as a graft. Patient preference also plays a major role in the type of treatment that is chosen, so it is important for patients to fully understand their options before making a decision.

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